POLYETHYLENIMINE INCREASES THE IMMUNOGENICITY OF DNA-VACCINE BASED ON THE THYROSINE HYDROXYLASE GENE IN THE MOUSE MODEL OF NEUROBLASTOMA
https://doi.org/10.29235/1814-6023-2018-15-3-323-330
Abstract
Neuroblastoma is one of the most common solid tumors in children with a poor prognosis at the IV stage. A common marker of neuroblastoma is a high expression of tyrosine hydroxylase.
DNA vaccination is a concomitant method of treatment of oncological diseases that are characterized by a high probability of long-term remission and a risk of subsequent relapse.
We performed the DNA vaccination of A/J mice using a tyrosine hydroxylase (TH) design as a tumor antigen. Polyethylenimine was used as a synthetic carrier for vaccine delivery. It was shown that the conjugation of the developed vaccine with polyethylenimine increases the vaccine immunogenicity, which is manifested both in slowing the tumor progression and in activating the cellular immunity, including the cytotoxic T-cell response and the gamma-interferon production.About the Authors
M. V. StegantsevaBelarus
Maria V. Stegantseva – Master of Biological Sciences, Researcher
43, Frunzenskaya Str., v. Borovliany, 223053, Minsk Region
V. A. Shinkevich
Belarus
Veronika A. Shinkevich – Junior researcher
43, Frunzenskaya Str., v. Borovliany, 223053, Minsk Region
K. P. Vashkevich
Belarus
Katsiaryna P. Vashkevich – Senior researcher
43, Frunzenskaya Str., v. Borovliany, 223053, Minsk Region
T. M. Mikhaleuskaya
Belarus
Taisiya M. Mikhaleuskaya – Pathomorphologist
43, Frunzenskaya Str., v. Borovliany, 223053, Minsk Region
A. N. Meleshko
Belarus
Alexander N. Meleshko – Ph. D. (Biol.), Head of the Laboratory
43, Frunzenskaya Str., v. Borovliany, 223053, Minsk Region
References
1. Cheung N.-K. V., Dyaer M. A. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nature Reviews Cancer, 2013, vol. 13, no. 6, pp. 397–411. https://doi.org/10.1038/nrc3526
2. Berzofsky J. A., Tereba M., Oh S., Belyakov I. M., Ahlers J. D., Janik J. E., Morris J. C. Progress on new vaccine strategies for the immunotherapy and prevention of cancer. Journal of Clinical Investigations, 2004, vol. 113, no. 11, pp. 1515– 1525. https://doi.org/ 10.1172/JCI200421926
3. Sukhareva Е. V., Kalinina Т. S., Bulygina V. V., Dygalo N. N. Tyrosine hydroxylase of the brain and its regulation by glucocorticoids. Vavilovskii zhurnal genetiki i selektsii = Vavilov Journal of genetics and breeding, 2016, vol. 20, no. 2, pp. 212–219 (in Russian).
4. Robles-Frías M., Segura D. I., Márquez C., Quiroga E., Álvarez A. M., Sáez C. Neuroblastoma initially presenting as a primary bone tumor: diagnostic value of molecular assays for tyrosine hydroxylase. Medical and Pediatric Oncology, 2003, vol. 40, no. 3, pp. 167–170. https://doi.org/10.1002/mpo.10119
5. Huebener N., Fest S., Strandsby A., Michalsky E., Preissner R., Zeng Y., Gaedicke G., Lode H. N. A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity. Molecular Cancer Therapy, 2008, vol. 7, no. 7, pp. 2241–2251. https://doi.org/10.1158/1535-7163.MCT-08-0109
6. Tissue expression of TH. Available at: http://www.proteinatlas.org/ENSG00000180176-TH/tissue (accessed 15.08.2017).
7. Van den Berg J. H., Nuijen B., Schumacher T. N., Haanen J. B. A. G., Storm G., Beijnen J. H., Hennink W. E. Synthetic vehicles for DNA vaccination. Journal of Drug Targeting, 2010, vol. 18, no. 1, pp. 1–14. https://doi.org/10.3109/ 10611860903278023
Review
For citations:
Stegantseva M.V., Shinkevich V.A., Vashkevich K.P., Mikhaleuskaya T.M., Meleshko A.N. POLYETHYLENIMINE INCREASES THE IMMUNOGENICITY OF DNA-VACCINE BASED ON THE THYROSINE HYDROXYLASE GENE IN THE MOUSE MODEL OF NEUROBLASTOMA. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2018;15(3):323-330. (In Russ.) https://doi.org/10.29235/1814-6023-2018-15-3-323-330